The objective of this work has been to develop and characterize a mouse epidermal cell culture model system for studying promoter-dependent preneoplastic progression and its prevention. Sensitivity of JB6 cells to promotions of anchor-age-independence extends to a variety of classes of tumor promoters including growth factors, benzoyl peroxide, Vinyl products, like di-2-ethylhexylphthalate, as well as phorbol esters. retinoic acid inhibits promotion of anchorage-independence by 12-0-tetradecanoylphorbol-13-acetate (TPA), but not by benzoyl peroxide or epidermal growth factor (EGF). A new inhibitor, trisialoganglioside (GT), blocks promotion by TPA and benzoyl peroxide. Thus, retinoic acid and GT may block different required events in promotion. Commitment to anchorage-independent transformation requires at least four days exposure to TPA. New efforts are now directed toward the development of a human model system for studying preneoplastic progression using cells from individuals genetically predisposed to cancer, with much the same emphasis on elucidating genetic and membrane determinants.